Rare Pulmonology News

Disease Profile

Desmosterolosis

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

ageofonset-infancy.svg

ICD-10

Q87.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

no.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

rnn-autosomalrecessive.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

no.svg

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

no.svg

Categories

Congenital and Genetic Diseases; Metabolic disorders; Musculoskeletal Diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 35107

Definition
Desmosterolosis is a very rare sterol biosynthesis disorder characterized by multiple congenital anomalies, failure to thrive, and intellectual disability, with elevated levels of desmosterol.

Epidemiology
Only 9 cases have been reported in the literature to date.

Clinical description
Desmosterolosis presents at birth with growth restriction, spasticity with variable degrees of hand contractures, either microcephaly or relative macrocephaly, and microretrognathia. Transient neonatal seizures, nystagmus, strabismus and failure to thrive are also seen in most cases. Intellectual disability occurs in all patients and is first noted by delayed milestones for speech and adaptive, fine and gross motor development. Less common manifestations reported include hirsutism, facial dysmorphism (downslanting palpebral fissures, bilateral epicanthal folds, submucous cleft palate, and thick alveolar ridges), sensorineural hearing loss, patent arterial duct, ambiguous genitalia, bilateral clubfeet, muscle wasting, and cutis aplasia. Optic atrophy, corpus callosum agenesis and loss of white matter are also noted.

Etiology
Desmosterolosis is due to mutations in the DHCR24 gene (1p32.3) encoding 3-beta-hydroxysterol delta-24-reductase. This enzyme catalyzes the conversion of desmosterol (the cholesterol precursor) to cholesterol, which is highly involved in embryonic development and morphogenesis. Reduced enzyme activity leads to the accumulation of desmosterol and a lack of cholesterol, disrupting antenatal and postnatal development.

Genetic counseling
Desmosterolosis is inherited in an autosomal recessive manner and genetic counseling is possible.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Absent septum pellucidum
0001331
Agenesis of corpus callosum
0001274
Bifid uvula
0000193
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Feeding difficulties
Feeding problems
Poor feeding

[ more ]

0011968
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Muscle stiffness
0003552
Retrognathia
Receding chin
Receding lower jaw
Weak chin
Weak jaw

[ more ]

0000278
Rigidity
Muscle rigidity
0002063
Severe short stature
Dwarfism
Proportionate dwarfism
Short stature, severe

[ more ]

0003510
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
Submucous cleft hard palate
0000176
30%-79% of people have these symptoms
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
Large earlobe
Fleshy earlobe
Fleshy earlobes
Prominent ear lobes
prominent ear lobules

[ more ]

0009748
Low-set, posteriorly rotated ears
0000368
Narrow mouth
Small mouth
0000160
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Short nose
Decreased length of nose
Shortened nose

[ more ]

0003196
Status epilepticus
Repeated seizures without recovery between them
0002133
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
Ventriculomegaly
0002119
5%-29% of people have these symptoms
Ambiguous genitalia
Ambiguous external genitalia
Ambiguous external genitalia at birth
Intersex genitalia

[ more ]

0000062
Anomalous pulmonary venous return
0010772
Dermal atrophy
Skin degeneration
0004334
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Epicanthus
Eye folds
Prominent eye folds

[ more ]

0000286
Frontal bossing
0002007
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Intestinal malrotation
0002566
Macrocephaly
Increased size of skull
Large head
Large head circumference

[ more ]

0000256
Macrogyria
0007227
Metatarsus adductus
Front half of foot turns inward
0001840
Micromelia
Smaller or shorter than typical limbs
0002983
Osteopetrosis
Harder, denser, fracture-prone bones
0011002
Pachygyria
Fewer and broader ridges in brain
0001302
Patent ductus arteriosus
0001643
Polymicrogyria
More grooves in brain
0002126
Prominent forehead
Pronounced forehead
Protruding forehead

[ more ]

0011220
Renal agenesis
Absent kidney
Missing kidney

[ more ]

0000104
Splenomegaly
Increased spleen size
0001744
Talipes
0001883
1%-4% of people have these symptoms
Abnormal circulating cholesterol concentration
Abnormality of cholesterol metabolism
0003107
Alveolar ridge overgrowth
Overgrowth of gum ridge
0009085
Ambiguous genitalia, female
Atypical appearance of female genitals
0000061
Ambiguous genitalia, male
Ambiguous genitalia in males
0000033
Aplasia/Hypoplasia of the corpus callosum
0007370
Bilateral talipes equinovarus
Club foot on both sides
0001776
Cleft palate
Cleft roof of mouth
0000175
Cupped ear
Cup-shaped ears
Simple, cup-shaped ears

[ more ]

0000378
Generalized osteosclerosis
0005789
Gingival fibromatosis
0000169
Global developmental delay
0001263
Hypoplastic nasal bridge
Decreased size of nasal bridge
Small bridge of nose
Small nasal bridge

[ more ]

0005281
Joint contracture of the hand

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Desmosterolosis. Click on the link to view a sample search on this topic.

Rare Pulmonology News